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| ID | Type | Description | Link |
|---|---|---|---|
| UG1HD112079 | U.S. NIH Grant/Contract | View source | |
| UG1HD112097 | U.S. NIH Grant/Contract | View source | |
| UG1HD112100 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
This is a pragmatic randomized multicenter, effectiveness study comparing active treatment of a symptomatic patent ductus arteriosus (sPDA) to expectant management. We hypothesize in premature infants with a sPDA, expectant management reduces the incidence proportion of death or BPD by 10% (from 50% to 40%) when compared to active treatment.
Participants with a sPDA allocated to the active treatment arm will receive intravenous administration of indomethacin or ibuprofen (depending on center preference). The decision to ligate will be left to the clinical team. Participants with a sPDA allocated to the expectant management arm will receive supportive care at the clinical team's discretion and will receive indomethacin/ibuprofen or ligation if the infant develops cardiopulmonary compromise. The decision to ligate will be left to the clinical team.
The primary endpoint for the study will be death or BPD (as assessed by the physiologic definition) at 36 weeks postmenstrual age (PMA).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Treatment Group | Active Comparator | Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. |
|
| Expectant Management Group | Active Comparator | Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active Treatment | Other | Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. If the infant receives both, it will be considered a protocol violation. |
| Measure | Description | Time Frame |
|---|---|---|
| Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA | A composite outcome for infants who were diagnosed with physiologic bronchopulmonary dysplasia (BPD) or died by 36 weeks postmenstrual age (PMA). Physiologic BPD is determined using existing Neonatal Research Network Generic Database criteria at 36 weeks PMA. Infants alive an in hospital are classified based on respiratory status at 36 weeks PMA or by a room air weaning challenge performed between 36 and 37 weeks PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks PMA. | Randomization to 36 weeks PMA |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality at 36 Weeks PMA | mortality assessed at 36 week postmenstrual age | birth to 36 week postmenstrual age |
| Mortality Before Discharge | mortality assessed prior to hospital discharge |
| Measure | Description | Time Frame |
|---|---|---|
| Necrotizing Enterocolitis (NEC) at Status (2 Years) | Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB | 26 months corrected age |
| Retinopathy of Prematurity at Status (2 Years) |
Inclusion Criteria:
Postnatal age 48 hours -21 days
Infant 22 0/7 to 28 6/7 weeks gestation at birth
sPDA, as defined as:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41364689 | Derived | Laughon MM, Thomas SM, Watterberg KL, Kennedy KA, Keszler M, Ambalavanan N, Davis AS, Slaughter JL, Guillet R, Colaizy TT, Cotten CM, Dhawan MA, Bose CL, Talbert J, Smucny S, Benitz WE, Rysavy MA, Ohls RK, Baserga MC, DeMauro SB, Jaleel M, Jackson WM, Carlo WA, Puopolo KM, Hibbs AM, Katheria A, Sanchez PJ, D'Angio CT, Patel RM, Johnson BA, Chock VY, Bhatt AJ, Merhar SL, Moore R, Laptook AR, Ghavam S, Fuller J, Vyas-Read S, Kicklighter SD, Steinbrekera B, Anderson K, Chandrasekharan PK, Wyckoff MH, Montoya C, Das A, Do B, Chang S, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. JAMA. 2026 Feb 17;335(7):588-599. doi: 10.1001/jama.2025.23330. |
| Label | URL |
|---|---|
| NRN Website | View source |
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Per NIH Data Sharing Plan
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One infant was randomized but withdrew consent for use of any data. This infant is included in the Period table below, but excluded from all analyses.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Treatment Group | Infants assigned to the active treatment group will receive indomethacin, ibuprofen or acetaminophen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin, ibuprofen, or acetaminophen will be left to the center, however, infants may only receive one or the other. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 19, 2020 | Mar 12, 2026 |
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|
| Expectant Management | Other | Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. |
|
| birth to 120 days of life |
| Bronchopulmonary Dysplasia - Physiological Test | BPD defined by the physiologic test of oxygen therapy | birth to 36 week postmenstrual age |
| Bronchopulmonary Dysplasia - NIH Consensus Definition | BPD defined by the NIH consensus definition of moderate or severe | birth to 36 week postmenstrual age |
| Necrotizing Enterocolitis (NEC) at 36 Weeks PMA | Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB | birth to 36 weeks post menstrual age |
| Retinopathy of Prematurity at 36 Weeks PMA | Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug | birth to 36 weeks post menstrual age |
| Receipt of Therapies Designed to Close the PDA | Defined as ligation or cardiac catheterization | birth to 120 days |
| Weight at 36 Weeks PMA | Weight assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age |
| Height at 36 Weeks PMA | Height assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age |
| Head Circumference at 36 Weeks PMA | Head Circumference assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age |
Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug
| 26 months corrected age |
| Weight at Status (2 Years) | Weight assessed at status (2 years) | 26 months corrected age |
| Height at Status (2 Years) | Height assessed at status (2 years) | 26 months corrected age |
| Head Circumference at Status (2 Years) | Head Circumference assessed at status (2 years) | 26 months corrected age |
| Neurodevelopmental Impairment (NDI) at Status (2 Years) | Severe NDI will be defined by any of the following: a Bayley Scales of Infant and Toddler Development (BSID) III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits. | 26 months corrected age |
| Palo Alto |
| California |
| 94304 |
| United States |
| Sharp Mary Birch Hospital for Women & Newborns | San Diego | California | 92123 | United States |
| Emory University | Atlanta | Georgia | 30303 | United States |
| Northwestern Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| University of Mississippi Medical Center - Children's of Mississippi | Jackson | Mississippi | 39216 | United States |
| University of New Mexico | Albuquerque | New Mexico | 87131 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| RTI International | Durham | North Carolina | 27705 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Medical Center | Cincinnati | Ohio | 45267 | United States |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| Research Institute at Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Brown University - Women and Infants Hospital of Rhode Island | Providence | Rhode Island | 02905 | United States |
| University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | 75235 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84108 | United States |
| FG001 |
| Expectant Management Group |
Infants assigned to the expectant management group will receive indomethacin, ibuprofen, or acetaminophen only if cardiopulmonary compromise occurs. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
One infant was randomized but withdrew consent for use of any data. This infant is excluded from all analyses.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Active Treatment Group | Infants assigned to the active treatment group will receive indomethacin, ibuprofen, or acetaminophen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin, ibuprofen, or acetaminophen will be left to the center, however, infants may only receive one or the other. |
| BG001 | Expectant Management Group | Infants assigned to the expectant management group will receive indomethacin, ibuprofen, or acetaminophen only if cardiopulmonary compromise occurs. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Gestational Age | Gestational age was based on the obstetric estimate (last menstrual period, obstetrical assessments, or early ultrasound). If that was not available or disagreed by more than two weeks with the neonatologist's assessment based on physical or neurologic exams, the neonatologist's estimate was used. If gestational age in days was not recorded, sites entered zero for days. | Median | Inter-Quartile Range | Weeks |
| |||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Mortality at 36 Weeks PMA | mortality assessed at 36 week postmenstrual age | Not Posted | birth to 36 week postmenstrual age | Participants | |||||||||||||||||
| Secondary | Mortality Before Discharge | mortality assessed prior to hospital discharge | Not Posted | birth to 120 days of life | Participants | |||||||||||||||||
| Secondary | Bronchopulmonary Dysplasia - Physiological Test | BPD defined by the physiologic test of oxygen therapy | Not Posted | birth to 36 week postmenstrual age | Participants | |||||||||||||||||
| Secondary | Bronchopulmonary Dysplasia - NIH Consensus Definition | BPD defined by the NIH consensus definition of moderate or severe | Not Posted | birth to 36 week postmenstrual age | Participants | |||||||||||||||||
| Secondary | Necrotizing Enterocolitis (NEC) at 36 Weeks PMA | Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB | Not Posted | birth to 36 weeks post menstrual age | Participants | |||||||||||||||||
| Secondary | Retinopathy of Prematurity at 36 Weeks PMA | Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug | Not Posted | birth to 36 weeks post menstrual age | Participants | |||||||||||||||||
| Secondary | Receipt of Therapies Designed to Close the PDA | Defined as ligation or cardiac catheterization | Not Posted | birth to 120 days | Participants | |||||||||||||||||
| Secondary | Weight at 36 Weeks PMA | Weight assessed at 36 weeks post menstrual age | Not Posted | birth to 36 weeks post menstrual age | Participants | |||||||||||||||||
| Other Pre-specified | Necrotizing Enterocolitis (NEC) at Status (2 Years) | Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Other Pre-specified | Retinopathy of Prematurity at Status (2 Years) | Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Other Pre-specified | Weight at Status (2 Years) | Weight assessed at status (2 years) | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Other Pre-specified | Height at Status (2 Years) | Height assessed at status (2 years) | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Other Pre-specified | Head Circumference at Status (2 Years) | Head Circumference assessed at status (2 years) | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Other Pre-specified | Neurodevelopmental Impairment (NDI) at Status (2 Years) | Severe NDI will be defined by any of the following: a Bayley Scales of Infant and Toddler Development (BSID) III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits. | Not Posted | 26 months corrected age | Participants | |||||||||||||||||
| Primary | Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA | A composite outcome for infants who were diagnosed with physiologic bronchopulmonary dysplasia (BPD) or died by 36 weeks postmenstrual age (PMA). Physiologic BPD is determined using existing Neonatal Research Network Generic Database criteria at 36 weeks PMA. Infants alive an in hospital are classified based on respiratory status at 36 weeks PMA or by a room air weaning challenge performed between 36 and 37 weeks PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks PMA. | An intent-to-treat (ITT) analysis which included all infant participants who were randomized and who provided outcome data. | Posted | Count of Participants | Participants | Randomization to 36 weeks PMA |
| ||||||||||||||
| Secondary | Height at 36 Weeks PMA | Height assessed at 36 weeks post menstrual age | Not Posted | birth to 36 weeks post menstrual age | Participants | |||||||||||||||||
| Secondary | Head Circumference at 36 Weeks PMA | Head Circumference assessed at 36 weeks post menstrual age | Not Posted | birth to 36 weeks post menstrual age | Participants |
Adverse events are reported from time of randomization to 36 completed weeks PMA.
A serious adverse events is defined as: resulting in death, is life-threatening, requires prolongation of hospitalization, resulting in persistent or significant disability/incapacity, or any other serious important medical events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active Treatment Group | Infants assigned to the active treatment group will receive indomethacin, ibuprofen, or acetaminophen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. | 23 | 240 | 43 | 240 | 3 | 240 |
| EG001 | Expectant Management Group | Infants assigned to the expectant management group will receive indomethacin, ibuprofen, or acetaminophen only if cardiopulmonary compromise occurs. | 10 | 241 | 32 | 241 | 9 | 241 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Necrotising enterocolitis neonatal | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Sepsis neonatal | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Neonatal intestinal perforation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Appendicitis perforated | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Group B streptococcus neonatal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia escherichia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Enterobacter pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fungal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Neonatal respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Neonatal respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Neonatal pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary haemorrhage neonatal | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Cardio-respiratory arrest neonatal | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Neonatal pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Cardiopulmonary failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac arrest neonatal | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Retinopathy of prematurity | Eye disorders | MedDRA | Systematic Assessment |
| |
| Hepatic infarction | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Posthaemorrhagic hydrocephalus | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Necrotising enterocolitis neonatal | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Neonatal pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pulmonary haemorrhage neonatal | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Neonatal sinus bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Splenic infarction | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Neonatal hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Matthew Laughon | University of North Carolina at Chapel Hill | (984) 974-7851 | matt_laughon@med.unc.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2025 | Mar 12, 2026 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 21, 2022 | Apr 6, 2026 | ICF_002.pdf |
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| D004374 | Ductus Arteriosus, Patent |
| D007232 | Infant, Newborn, Diseases |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D057832 | Watchful Waiting |
| ID | Term |
|---|---|
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
|
|